Many studies demonstrate that environmental chemicals impair the mammalian immune system. Mechanisms responsible for this immunotoxicity are poorly understood. Furthermore, little is known about the effects of environmental chemicals on lymphopoiesis, the process of lymphocyte development. To model the effects of ubiquitous environmental chemicals on blood cell development we have studied the modulation of B lymphocyte development by polycyclic aromatic hydrocarbons (PAH) in long term, murine bone marrow cultures. This simulation of B lymphopoiesis is invaluable since it closely mimics conditions required in vivo for B cell development and because it has yielded a large database on cell surface adhesion molecules and soluble factors (cytokines) required for B cell growth and differentiation. Previous studies revealed 2 levels at which PAH alter B cell development in bone marrow cultures. Within 12 hours of PAH exposure preB cells commit suicide by a process known as programmed cell death or apoptosis. In some cases cell death is initiated at extremely low PAH doses (10-8M). Curiously, PAH induced programmed cell death closely resembles the process by which developing immune systems are purged of pathologic autoimmune lymphocytes, the implication being that xenobiotic exposure during development could preempt autoimmune clonal deletion and thereby potentiate autoimmune disease. Cell populations surviving this initial lymphotoxic phase exhibit altered growth, survival, and maturational characteristics. Since the immune system begins to program responsiveness to a constellation of antigenic insults at this developmental stage these results suggest that PAH exposure could compromise immune defenses against microbes and against tumors, induced in part as a result of environmental chemical exposure. Given the importance of these findings to environmental health 2 specific goals are proposed: 1) to delineate the intracellular mechanisms controlling PAH induced programmed cell death and 2) to determine how preB cell interactions with the bone marrow microenvironment are altered by exposure to PAH. Proposed studies will emphasize the similarities between PAH-induced programmed cell death and the process of autoimmune clonal deletion as well as determine the extent to which PAH impair lymphopoiesis by modifying adhesion molecule function, cytokine production, and/or cytokine responsiveness.